[75Se]-selenohomotaurocholic acid degradation by bacterial enzymes in vitro and in vivo. Is it still a specific indicator for active ileal bile acid uptake?
The stability of the bile acid analogue [75Se]-selenohomotaurocholic acid (75SeH-CAT) was studied in man. When 75SeHCAT was administered to patients for diagnostic purposes the majority of labeled material present in the feces was found deconjugated. In vitro incubation of 75SeHCAT, by addition of fecal homogenate or with addition of purified enzyme, showed identical deconjugation. The relative differences in polarities of 75SeHCAT, [75Se]-selenohomocholic acid (75SeHCA), [14C]-taurocholic acid (14C-TCA) and [14C]-cholic acid (14C-CA) were estimated by isoelectric focusing and selective chloroform extractions at various pH values. The pI values representing the pH where these molecules become uncharged were for 75SeHCA and 75SeHCAT 3.1, for 14C-TCA 3.0 and for 14C-CA 3.9. These results suggest that from these bile acids only 14C-CA is a candidate for passive absorption in the colon, while 75SeHCA would be far too polar for passive diffusion. Indeed, we could demonstrate the inability of 75SeHCA for passive absorption in healthy persons. In conclusion, 75SeHCAT, specifically selected to monitor active ileal bile acid transport, functions as a good indicator of this process in its conjugated form. In contrast to published data it is susceptible to bacterial degradation, and therefore gives rise to a diminished whole-body retention.
van den Berg
J W
JW
Department of Internal Medicine II, Erasmus University Rotterdam, The Netherlands.
de Rooij
F W
FW
Bosman-Jacobs
E P
EP
D000581:Amidohydrolases / Q000378:metabolism*; D001419:Bacteria / Q000201:enzymology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D004764:Enterohepatic Circulation; D005243:Feces / Q000382:microbiology; D006801:Humans; D007082:Ileum / Q000378:metabolism; D066298:In Vitro Techniques; D013656:Taurocholic Acid / Q000031:analogs & derivatives*
D001647:Bile Acids and Salts; D013656:Taurocholic Acid; C033638:23-seleno-25-homotaurocholic acid; D000581:Amidohydrolases; C023154:choloylglycine hydrolase